Effects of trypan blue on the action of adrenergic agonists in the guinea-pig isolated atrium.

It has been reported that trypan blue, a diazo dye with polyamphipathic structure, can inhibit the coupling of receptors to G-proteins. The present study was carried out to investigate the effect of trypan blue on the actions of adrenoceptor agonists in the guinea-pig atrium. Trypan blue (10 and 100 microM) antagonized the positive inotropic effects of isoprenaline and dobutamine by shifting their concentration-response curves to the right. With the selective beta 2-adrenoceptor agonist, salbutamol, there was a reduction of response in the presence of trypan blue. Therefore, we concluded that trypan blue diminish the response to beta-adrenoceptor agonists possibly via decoupling receptors from Gs. Trypan blue and similar agents, due to their unique mode of action, can be used as tools for the investigation of the mechanism of receptor-G protein coupling in the whole tissue preparation.

The bioavailability of griseofulvin from microsized and ultramicrosized tablets in nonfasting volunteers.

Tablets of either microsized or ultramicrosized griseofulvin (2 x 125 mg), were administered to 6 healthy volunteers of either sex just before a breakfast containing 4o g. of butter. The plasma concentration of griseofulvin were determined 1, 3, 5, 7, 9, 24, and 32 h. after dosing using a spectrofluorometric method, and pharmacokinetic parameters (Cp max, t max, AUC 0 - greater than 32) were calculated. These parameters were found to be; Cp max = 0.0.681 +/- 0.1 mu/ml, t max. = 2.51 +/- 0.33 h. and AUC = 14.14 +/- 2.33 micrograms h/ml for microsized tablets and Cp max = 0.80 +/- 0.08 +/- g/ml, t max = 2.44 +/- 0.54 and AUC = 16.25 +/- 1.16 microgram h/ml for ultramicrosized tablets. Our results show that mean peak plasma level and AUC (0 - greater than 32) are only slightly higher for the ultramicrosized preparation and the time to peak plasma level is similar in two preparations. Therefore, it is concluded that coadministration of griseofulvin with food will tend to reduce the difference between the bioavailability of the two type of preparations.

Inhibitory action of aminoglycoside antibiotics on the electrically induced release of opioid peptides in the guinea-pig ileum in vitro.

The effect of aminoglycoside antibiotics upon the electrically induced release of endogenous opioid peptides from the guinea-pig ileum was studied in vitro. Stimulation of guinea pig ileum at 10 Hz in normal Tyrode solution resulted in the naloxone sensitive depression of the twitch contractions of this muscle. Addition of aminoglycosides during 10 Hz stimulation diminished this naloxone sensitive depression in a dose dependent manner. IC50s of this effect of streptomycin, neomycin, kanamycin and gentamicin were found to be 2.54, 2.29, 1.36 and 0.7 mg/ml respectively. A 3.5 fold increase in the calcium concentration of media during 10 Hz stimulation significantly reversed the effect of aminoglycosides. It is concluded that aminoglycoside antibiotics exert their effect by interfering with trans-membrane movements of calcium at the nerve endings which is required for the electrically induced release of opioid peptides.